Phase III Clinical Study on the Efficacy and Safety of Semaglutide and Ozempic® in Patients With Type 2 Diabetes

Prior treatment

• Received hypoglycemic drugs other than metformin (including Chinese medicine) within 8 weeks before randomization;
• Diabetic ketoacidosis or hyperglycemic hyperosmolar state within 3 months before randomization;
• Cardiovascular diseases such as acute coronary syndrome (including but not limited to acute myocardial infarction, or unstable angina), arrhythmia requiring treatment, severe heart failure (refer to New York Heart Association heart function grade III or IV), coronary artery bypass grafting or coronary stent implantation within 6 months before screening;
• New cerebrovascular accident (including ischemic stroke, hemorrhagic stroke and transient ischemic attack, etc.) within 6 months before screening;
• Severe trauma or severe infection or surgery that may affect blood sugar control within 1 month before screening;
• History of cholecystitis due to cholelithiasis or other reasons within 6 months before screening;
• Donated blood or lost ≥400mL of blood within 3 months before screening, or received blood transfusion therapy, or planned to donate blood during the trial;
• Received other clinical research drugs or device treatments within 3 months before screening, or participated in other drug clinical trials and are still within 5 half-lives of the trial drug, whichever is older; or planned to participate in other clinical studies during the trial;
• Have a history of drug abuse (including drug abuse) and/or alcohol dependence within 6 months before screening;
• Male and female research participants who have fertility plans during the trial and within 2 months after the last dose of the trial drug, or are unwilling to take reliable contraceptive measures for contraception;

Other illness

• Type 1 diabetes, special type of diabetes;
• Has a history of ≥2 episodes of grade 3 hypoglycemia within 1 year before randomization;
• Severe complications of diabetes at screening: such as proliferative diabetic retinopathy, macular edema; history of renal transplantation; severe peripheral vascular disease (such as amputation, chronic foot ulcers, intermittent claudication);
• Untreated or poorly controlled hypertension (defined as systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg) at screening/randomization;
• History of acute or chronic pancreatitis;
• Cushing's syndrome, hyperthyroidism, and uncontrolled hypothyroidism at screening;
• Significant gastric emptying abnormalities (such as gastric outlet obstruction) and severe gastrointestinal diseases at screening;
• History or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2);
• History of malignant tumors in the past 5 years (regardless of organ system, whether treated or not, and whether there is evidence of recurrence or metastasis) or currently being evaluated for potential malignant tumors, but excluding clinically cured cervical carcinoma in situ and skin basal cell carcinoma;
• Known allergy to any component of semaglutide injection or allergy to other GLP-1 RA drugs;
• Mental disorder or language barrier, unable to fully understand and cooperate;

Lab values

• Used non-diabetes treatment drugs that may have a significant impact on glucose metabolism for 1 week or more within 3 months before randomization, such as glucocorticoids (systemic glucocorticoids used for \<7 days, excluding inhalation, ocular medication or topical application), sympathetic nerve stimulants (such as isoproterenol, dopamine, atropine, etc.), growth hormone, high-dose salicylates (300 mg/day and above), danazol, octreotide and anabolic androgenic steroids (such as oxymetholone, oxandrolone, etc.);
• Any disease that may cause hemolysis or red blood cell instability and affect HbA1c detection, such as blood system tumors, hemolytic anemia, sickle cell disease;
• Meet any of the following criteria at screening:
  • Liver function impairment: ALT or AST ≥ 5 times the upper limit of normal, or total bilirubin ≥ 2 times the upper limit of normal; Renal function impairment: glomerular filtration rate (eGFR, CKD-EPI formula) \< 45mL/min/1.73m2; Fasting triglyceride (TG) ≥ 5.7mmol/L after stable medication; Calcitonin ≥ 50ng/L; Hemoglobin ≤ 100g/L; Thyrotropin (TSH) \> 6mIU/L after stable medication; Blood amylase or lipase ≥ 3 times the upper limit of normal; Hepatitis C virus antibody, human immunodeficiency virus antibody, syphilis serological test results are positive, hepatitis B virus surface antigen is positive and HBV-DNA is positive.

Other

• Pregnant or lactating women;
• Other situations that the researcher considers unsuitable for participation in this study. -

• 1\) Voluntary signing of informed consent; 2) Aged 18-75 years (inclusive) at the time of signing the informed consent, male or female; 3) Diagnosed with type 2 diabetes according to the WHO diabetes diagnostic criteria; 4) Laboratory tests at the research center at screening: 7.5%≤HbA1c≤10.5%; 5) Before randomization, study participants received stable doses of metformin (≥1500mg/day or maximum tolerated dose: \<1500mg/day, but ≥1000mg/day) for at least 8 weeks (maximum tolerated dose must be supported by previous medical records); 6) Body mass index (BMI) ≥18.5kg/m2 and ≤35.0kg/m2 at screening; 7) Willing and able to undergo treatment and follow-up as required by the protocol.